Synthesis of methylenedioxy-bearing 1-aryl-3-carboxylisoquinolines using a modified Ritter reaction procedure

This paper describes original approaches aimed at the preparation of electron-rich 1-aryl-3-carboxylisoquinolines. Our first attempt led to an efficient preparation of 1-hydroxyisoquinoline-3-carboxylic acid methyl ester starting from bromophthalide via a rearrangement of 2-acetylamino-2-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-malonic acid dimethyl ester. However, as its eventual application to the synthesis of methylenedioxy-bearing substrates seemed rather long, a second approach involving an extension of the Ritter reaction to safrole was devised. We thus report that, under proper experimental settings, the use of 54% tetrafluoroboric acid in ether enables a Ritter reaction between safrole and 3,4,5-trimethoxybenzonitrile yielding 17% of 7-methyl-5-(3,4,5-trimethoxyphenyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinoline. This acidic reagent avoids the extensive decomposition seen when using the classical Ritter reaction conditions (i.e.: concentrated sulfuric acid). Further chemical transformations of this methyl-bearing dihydroisoquinoline led to the methylenedioxy-bearing 1-aryl-3-carboxylisoquinoline. These derivatives are related to the peripheral benzodiazepine receptor ligand PK 11195 as well as falcipain-2 inhibitors and other potential antitumor agents.     

Human immunoglobulin adsorption investigated by means of quartz crystal microbalance dissipation, atomic force microscopy, surface acoustic wave, and surface plasmon resonance techniques

Time-resolved adsorption behavior of a human immunoglobin G (hIgG) protein on a hydrophobized gold surface is investigated using multitechniques: quartz crystal microbalance/dissipation (QCM-D) technique; combined surface plasmon resonance (SPR) and Love mode surface acoustic wave (SAW) technique; combined QCM-D and atomic force microscopy (AFM) technique. The adsorbed hIgG forms interfacial structures varying in organization from a submonolayer to a multilayer. An "end-on" IgG orientation in the monolayer film, associated with the surface coverage results, does not corroborate with the effective protein thickness determined from SPR/SAW measurements. This inconsistence is interpreted by a deformation effect induced by conformation change. This conformation change is confirmed by QCM-D measurement. Combined SPR/SAW measurements suggest that the adsorbed protein barely contains water after extended contact with the hydrophobic surface. This limited interfacial hydration also contributed to a continuous conformation change in the adsorbed protein layer. The viscoelastic variation associated with interfacial conformation changes induces about 1.5 times overestimation of the mass uptake in the QCM-D measurements. The merit of combined multitechnique measurements is demonstrated.     

Theoretical Evaluation of Steric Effects in [ReH(5)(PR(3))(2)(SiR(3))(2)] Complexes with the IMOMM Method

A theoretical study including full geometry optimizations is carried out at the IMOMM(MP2:MM3) (IMOMM = integrated molecular orbital molecular mechanics) computational level on the [ReH(5)(PPh(i)()Pr(2))(2)(SiHPh(2))(2)] and [ReH(5)(PCyp(3))(2)(SiH(2)Ph)(2)] systems, the results being compared with available experimental diffraction data, as well as with MP2 results on the model system [ReH(5)(PH(3))(2)(SiH(3))(2)]. A simple scheme for the analysis of the relative weight of different contributions to the "steric" distortion is also proposed and applied to the same [ReH(5)(PPh(i)()Pr(2))(2)(SiHPh(2))(2)] and [ReH(5)(PCyp(3))(2)(SiH(2)Ph)(2)] species.     

Syntheses and structural studies on two cycloruthenapentadienyl complexes: [(CO)3RuC4(CH2OH)4]Ru(CO)3·H2O and [(CO)3RuC4(CH2CH2OH)2(C2H5)2]Ru(CO)3

Syntheses and single-crystal X-ray diffraction studies have been completed on two cycloruthenapentadienyl (CO)₆Ru₂L₂ derivatives, with L = CH₂OHC = CCH₂OH and C₂H₅C=CCH₂CH₂OH respectively. Crystal data are as follows: for [(CO)₃RuC₄(CH₂OH)₄]Ru(CO)₃·H₂O, P2₁/c, a 13.72(1), b 9.501(4), c 14.86(1) Å, β 101.10(6)°, R_w = 0.052 for 1911 reflections; for [(CO)₃RuC₄(CH₂CH₂OH)₂(C₂H₅)₂]Ru(CO)₃, P2₁/c, a 9.191(3), b 16.732(4), c 14.903(3) Å, β 113.61(4)°, R_w = 0.042 for 2865 reflections. Both compounds are built up from binuclear units, each unit being regarded as a Ru(CO)₃ fragment π-bonded to a cycloruthenapentadienyl ring. The molecular parameters are compared with those of known cyclometallapentadienyl complexes of transition metals. The presence of a semi-bridging CO group is discussed.     

Persistent (amino)(silyl)carbenes

(Amino)(silyl)carbenes, prepared by substitution reactions at a carbene center, can survive several days at 0 degrees C. These species are not push-pull carbenes as their phosphino analogues and therefore are excellent ligands for transition-metal centers.     

Settling of paraffin crystals in cooled middle distillate fuels

The mechanism of action of additives that control the sedimentation of paraffin crystals after their crystallization in model diesel oil has been studied by means of a new experimental approach. The chemical analysis of the crystals and detailed measurements of the sedimentation phenomenon give new insights into this complex process. Thus, the wax antisettling additives used for preventing wax crystal sedimentation adsorb at the surfaces of wax particles and provide them with enhanced colloidal stability. The settling rate is not related to the size of the crystals or the viscosity of the liquid medium, but to the ability of the additives to prevent the aggregation of wax crystals. The reported methodology makes it possible to investigate the fundamental mechanisms, but also to evaluate structure-activity relationships of the various additives used in the petroleum industry.     

Spectrophotometric and Nuclear Magnetic Resonance Study of Temperature- and Pressure-induced Changes in the Intimate Solvation of Neodymium (III) in N,N-Dimethylformamide and Trimethylphosphate

The temperature- and pressure-dependent equilibria for the addition of an extra N, N-dimethylforrnamide (DMF) or trimethylphosphate (TMP) ligand onto [Nd (DMF)₈]³⁺- and [Nd(TMP)₆]³⁺-species respectively have been measured by visible spectrophotometry. Complementary NMR. studies on other lanthanide ions show a gradual shift in preference for the lower coordination number across the lanthanide series.